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Revisiting potential druggable targets againstSARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review

DRUG DEVELOPMENT RESEARCH (2020)

Journal

DRUG DEVELOPMENT RESEARCH

Volume 81, Issue 8, Pages 919-941

Publisher

WILEY

DOI: 10.1002/ddr.21709

Keywords

clinical trial; COVID-19; drug repurposing; drug targets; therapeutics; vaccines

Categories

Chemistry, Medicinal Pharmacology & Pharmacy

Funding

Ministry of Science, ICT and Future Planning
National Research Foundation of Korea
Korea Research Fellowship Program [2018H1D3A1A01074712]

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Abstract

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID-19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS-CoV-2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target-based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti-SARS-CoV-2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS-CoV-2 infection.

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Mokdad, Sara Momtazmanesh, Lorenzo Monasta, Md Moniruzzaman, Ute Mons, Fateme Montazeri, AmirAli Moodi Ghalibaf, Yousef Moradi, Maryam Moradi, Mostafa Moradi Sarabi, Negar Morovatdar, Shane Douglas Morrison, Jakub Morze, Elias Mossialos, Ebrahim Mostafavi, Ulrich Otto Mueller, Francesk Mulita, Admir Mulita, Efren Murillo-Zamora, Kamarul Imran Musa, Julius C. Mwita, Shankar Prasad Nagaraju, Mohsen Naghavi, Firzan Nainu, Tapas Sadasivan Nair, Hastyar Hama Rashid Najmuldeen, Vinay Nangia, Shumaila Nargus, Abdallah Y. Naser, Hasan Nassereldine, Zuhair S. Natto, Javaid Nauman, Biswa Prakash Nayak, Rawlance Ndejjo, Hadush Negash, Ruxandra Irina Negoi, Hau Thi Hien Nguyen, Dang H. Nguyen, Phat Tuan Nguyen, Van Thanh Nguyen, Hien Quang Nguyen, Robina Khan Niazi, Yeshambel T. Nigatu, Dina Nur Anggraini Ningrum, Muhammad A. Nizam, Lawrence Achilles Nnyanzi, Mamoona Noreen, Jean Jacques Noubiap, Ogochukwu Janet Nzoputam, Chimezie Igwegbe Nzoputam, Bogdan Oancea, Nkechi Martina Odogwu, Oluwakemi Ololade Odukoya, Vivek Anand Ojha, Hassan Okati-Aliabad, Akinkunmi Paul Okekunle, Osaretin Christabel Okonji, Patrick Godwin Okwute, Isaac Iyinoluwa Olufadewa, Obinna E. Onwujekwe, Michal Ordak, Alberto Ortiz, Uchechukwu Levi Osuagwu, Abderrahim Oulhaj, Mayowa O. Owolabi, Alicia Padron-Monedero, Jagadish Rao Padubidri, Raffaele Palladino, Demosthenes Panagiotakos, Songhomitra Panda-Jonas, Ashok Pandey, Anamika Pandey, Seithikurippu R. Pandi-Perumal, Anca Mihaela Pantea Stoian, Shahina Pardhan, Tarang Parekh, Utsav Parekh, Maja Pasovic, Jay Patel, Jenil R. Patel, Uttam Paudel, Veincent Christian Filipino Pepito, Marcos Pereira, Norberto Perico, Simone Perna, Ionela-Roxana Petcu, Fanny Emily Petermann-Rocha, Vivek Podder, Maarten J. Postma, Ghazaleh Pourali, Naeimeh Pourtaheri, Elton Junio Sady Prates, Mirza Muhammad Fahd Qadir, Ibrahim Qattea, Pourya Raee, Ibrar Rafique, Mehran Rahimi, Mahban Rahimifard, Vafa Rahimi-Movaghar, Md Obaidur Rahman, Muhammad Aziz Rahman, Mohammad Hifz Ur Rahman, Mosiur Rahman, Md Mosfequr Rahman, Mohamed Rahmani, Shayan Rahmani, Vahid Rahmanian, Setyaningrum Rahmawaty, Niloufar Rahnavard, Bibek Rajbhandari, Pradhum Ram, Sheena Ramazanu, Juwel Rana, Nemanja Rancic, Muhammad Modassar Ali Nawaz Ranjha, Chythra R. Rao, Deepthi Rapaka, Drona Prakash Rasali, Sina Rashedi, Vahid Rashedi, Ahmed Mustafa Rashid, Mohammad-Mahdi Rashidi, Zubair Ahmed Ratan, Salman Rawaf, Lal Rawal, Elrashdy Moustafa Mohamed Redwan, Giuseppe Remuzzi, Kannan R. R. Rengasamy, Andre M. N. Renzaho, Luis Felipe Reyes, Nima Rezaei, Nazila Rezaei, Mohsen Rezaeian, Hossein Rezazadeh, Seyed Mohammad Riahi, Yohanes Andy Rias, Muhammad Riaz, Daniela Ribeiro, Monica Rodrigues, Jefferson Antonio Buendia Rodriguez, Leonardo Roever, Peter Rohloff, Gholamreza Roshandel, Abazar Roustazadeh, Godfrey M. Rwegerera, Aly M. A. Saad, Maha Mohamed Saber-Ayad, Siamak Sabour, Leila Sabzmakan, Basema Saddik, Erfan Sadeghi, Umar Saeed, Sahar Saeedi Moghaddam, Sare Safi, Sher Zaman Safi, Amene Saghazadeh, Narjes Saheb Sharif-Askari, Fatemeh Saheb Sharif-Askari, Amirhossein Sahebkar, Soumya Swaroop Sahoo, Harihar Sahoo, K. M. Saif-Ur-Rahman, Mirza Rizwan Sajid, Sarvenaz Salahi, Saina Salahi, Mohamed A. Saleh, Mohammad Amin Salehi, Joshua A. Salomon, Juan Sanabria, Rama Krishna Sanjeev, Francesco Sanmarchi, Milena M. Santric-Milicevic, Made Ary Sarasmita, Saman Sargazi, Brijesh Sathian, Thirunavukkarasu Sathish, Monika Sawhney, Markus P. Schlaich, Maria Ines Schmidt, Art Schuermans, Abdul-Aziz Seidu, Nachimuthu Senthil Kumar, Sadaf G. Sepanlou, Yashendra Sethi, Allen Seylani, Maryam Shabany, Tahereh Shafaghat, Melika Shafeghat, Mahan Shafie, Nilay S. Shah, Samiah Shahid, Masood Ali Shaikh, Mohd Shanawaz, Mohammed Shannawaz, Sadaf Sharfaei, Bereket Beyene Shashamo, Rahman Shiri, Aminu Shittu, K. M. Shivakumar, Siddharudha Shivalli, Parnian Shobeiri, Fereshteh Shokri, Kerem Shuval, Migbar Mekonnen Sibhat, Luis Manuel Lopes Rodrigues Silva, Colin R. Simpson, Jasvinder A. Singh, Paramdeep Singh, Surjit Singh, Md Shahjahan Siraj, Anna Aleksandrovna Skryabina, Abdullah Al Mamun Sohag, Hamidreza Soleimani, Solikhah Solikhah, Mohammad Sadegh Soltani-Zangbar, Ranjani Somayaji, Reed J. D. Sorensen, Antonina V. Starodubova, Sujata Sujata, Muhammad Suleman, Jing Sun, Johan Sundstrom, Rafael Tabares-Seisdedos, Seyyed Mohammad Tabatabaei, Seyed-Amir Tabatabaeizadeh, Mohammad Tabish, Majid Taheri, Ensiyeh Taheri, Elahe Taki, Jacques J. L. Lukenze Tamuzi, Ker-Kan Tan, Nathan Y. Tat, Birhan Tsegaw Taye, Worku Animaw Temesgen, Mohamad-Hani Temsah, Riki Tesler, Pugazhenthan Thangaraju, Kavumpurathu Raman Thankappan, Rajshree Thapa, Samar Tharwat, Nihal Thomas, Jansje Henny Vera Ticoalu, Amir Tiyuri, Marcello Tonelli, Marcos Roberto Tovani-Palone, Domenico Trico, Indang Trihandini, Jaya Prasad Tripathy, Samuel Joseph Tromans, Guesh Mebrahtom Tsegay, Abdul Rohim Tualeka, Derara Girma Tufa, Stefanos Tyrovolas, Sana Ullah, Era Upadhyay, Seyed Mohammad Vahabi, Asokan Govindaraj Vaithinathan, Rohollah Valizadeh, Kim Robin van Daalen, Priya Vart, Shoban Babu Varthya, Tommi Juhani Vasankari, Siavash Vaziri, Madhur Verma Verma, Georgios-Ioannis Verras, Danh Cao Vo, Birhanu Wagaye, Yasir Waheed, Ziyue Wang, Yanqing Wang, Cong Wang, Fang Wang, Gizachew Tadesse Wassie, Melissa Y. Wei Wei, Abrha Hailay Weldemariam, Ronny Westerman, Nuwan Darshana Wickramasinghe, Yifan Wu, Ratna D. W. I. Wulandari, Juan Xia, Hong Xiao, Suowen Xu, Xiaoyue Xu, Dereje Y. Yada, Lin Yang, Hiroshi Yatsuya, Metin Yesiltepe, Siyan Yi, Hunachew Kibret Yohannis, Naohiro Yonemoto, Yuyi You, Sojib Bin Zaman, Nelson Zamora, Iman Zare, Kourosh Zarea, Armin Zarrintan, Mikhail Sergeevich Zastrozhin, Naod Gebrekrstos Zeru, Zhi-Jiang Zhang, Chenwen Zhong, Jingjing Zhou, Magdalena Zielinska, Yossef Teshome Zikarg, Sanjay Zodpey, Mohammad Zoladl, Zhiyong Zou, Alimuddin Zumla, Yves Miel H. Zuniga, Dianna J. Magliano, Christopher J. L. Murray, Simon I. Hay, Theo Vos

Summary: Diabetes is a major global cause of death and disability, with the total prevalence expected to continue to rise globally by 2050. Type 2 diabetes accounts for the majority of diabetes cases, largely due to obesity caused by multiple factors.

LANCET (2023)

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Article Multidisciplinary Sciences

Evolutionary trend of bovine ?-defensin proteins toward functionality prediction: A domain-based bioinformatics study

Saiful Islam, Mst Rubaiat Nazneen Akhand, Mahmudul Hasan

Summary: Defensins are small cationic peptides with a three-dimensional beta-strand structure connected by disulfide bonds. They are key elements of the innate immune system and have diverse roles in various animals. However, the genomic information about beta-defensins in cattle is insufficient and the functions of defensins in the immune system are still unclear. Our study investigated the evolutionary relations of bovine defensin proteins with those of humans and revealed significant domain variation in different clusters. The proteins show different patterns of disulfide bridges and may have specialized functions in combating pathogens.

HELIYON (2023)

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Editorial Material Chemistry, Medicinal

FDA Modernization Act 2.0: An insight from nondeveloping country

Sajidur Rahman Akash, M. A. Jobayer Billah Arnob, Md Jamal Uddin

Summary: Animal testing is crucial for evaluating the efficacy and safety of medications in drug development research. However, the newly introduced Food and Drug Administration Modernization Act 2.0 offers alternative testing methods that do not involve animal testing, potentially impacting nondeveloped countries worldwide. This study explores the implications of this act, including in silico modeling, human tissue-on-chip engineering, animal-free recombinant antibodies, tissue engineering, and artificial intelligence.

DRUG DEVELOPMENT RESEARCH (2023)

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Article Biochemistry & Molecular Biology

Differential Effects of the Processed and Unprocessed Garlic (Allium sativum L.) Ethanol Extracts on Neuritogenesis and Synaptogenesis in Rat Primary Hippocampal Neurons

Yeasmin Akter Munni, Raju Dash, Ho Jin Choi, Sarmistha Mitra, Md. Abdul Hannan, Kishor Mazumder, Binod Timalsina, Il Soo Moon

Summary: Garlic extracts, both processed and unprocessed, have been found to promote the maturation of hippocampal neurons and the formation of functional synapses. The compound linalool, found in both extracts, plays a role in promoting neurite outgrowth and has a modulatory effect on neurotrophic signaling pathways.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Biochemistry & Molecular Biology

Immunoinformatics for Novel Multi-Epitope Vaccine Development in Canine Parvovirus Infections

Bashudeb Paul, Jahangir Alam, Mridha Md. Kamal Hossain, Syeda Farjana Hoque, Md. Nazmul Islam Bappy, Hafsa Akter, Nadim Ahmed, Margia Akter, Mohammad Ali Zinnah, Shobhan Das, Md. Mukthar Mia, Md. Shafiullah Parvej, Sonjoy Sarkar, Hiren Ghosh, Mahmudul Hasan, Hossam M. Ashour, Md. Masudur Rahman

Summary: In this study, a multi-epitope vaccine against canine parvovirus (CPV-2) was designed using in silico approaches. Ten highly antigenic epitopes were selected and linked to a vaccine candidate with 272 nucleotides. The results suggest that this vaccine construct may be useful in preventing canine parvoviral enteritis (CPE) in dogs.

BIOMEDICINES (2023)

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